A 2-part, Phase 1b Clinical Study Designed to Evaluate the Safety, PK, and Efficacy of CRB-913 in Participants With Obesity

A Phase 1b, Randomized, Double-Blind, Placebo-Controlled, Dose-Range Finding Study of the Efficacy, Safety, and Pharmacokinetics of CRB-913 in Participants With Obesity With a Single Cohort Open-label Exploratory Pharmacokinetic Lead-In

This study will assess the safety of the investigational drug CRB-913 and how it is processed in the body.

The study has two parts: Part 1 will measure drug levels in healthy adults after taking CRB-913 tablets, and Part 2 will compare three doses of CRB-913 with placebo to evaluate safety, effects on body weight, and drug levels in the blood.

Part 2 is blinded, meaning participants, study doctors, and the sponsor will not know which treatment is given.

Participants in Part 2 will take study treatment for 12 weeks and will be followed for 28 days after treatment ends.

CRB-913 is a novel cannabinoid receptor type 1 (CB1) inverse agonist (CB1-IA) that is being developed for once-daily treatment of obesity.

This study will look at how the investigational drug CRB-913 behaves in the body and how it affects body weight.

The study has two parts:

Part 1 will include healthy adult participants. They will receive CRB-913 in tablet form. Researchers will measure how much of the drug enters the bloodstream and how long it stays there.

Part 2 will include participants who will receive one of three different doses of CRB-913 or a placebo (a tablet with no active drug). This part of the study will look at the safety of CRB-913 and its effects on body weight. Researchers will also measure the amount of CRB-913 in the blood.

Part 2 is blinded, which means that participants, study doctors, and the study sponsor will not know who is receiving CRB-913 or placebo.

All participants in Part 2 will take their assigned study tablets for 12 weeks, followed by a 28-day follow-up period after treatment ends.

The information collected in this study will help determine whether CRB-913 is safe, how the body processes it, and whether it may help with weight-related outcomes.

Inclusion Criteria:

• Part 1: Participants with BMI 18.0-25.0 kg/m²
• Part 2: Obese participants with BMI ≥30 kg/m²

Exclusion Criteria:

• Significant liver disease or moderate-severe hepatic impairment
• History of seizures, epilepsy, or intracranial surgery
• Diabetes mellitus (Type 1 or Type 2), except gestational
• Bariatric surgery or >5 kg weight change in past 3 months
• Recent use (within 3 months) of GLP-1 agonists or other weight-loss medications
• Major depression within 2 years.
• Any history of suicidal ideation/attempt
• Severe psychiatric disorders (e.g., schizophrenia, bipolar disorder)
• Elevated screening scores: PHQ-9 >4, GAD-7 >4, or positive C-SSRS Items 1-2
• Active or recent (within 5 years) malignancy (exceptions: in situ and fully resected nonmelanoma skin cancer)
• Abnormal thyroid function: TSH >6 mIU/L unless stable on replacement therapy
• QTc >470 msec (females) or >450 msec (males) or history of long QT syndrome
• Use of systemic corticosteroids or unstable chronic medications affecting BP, lipids, or glucose
• Use of CYP3A4 substrates or strong P-gp substrates/inhibitors
• Investigational drug use within 28 days
• Prior exposure to CRB-913 or other CB1 inverse agonists/antagonists
• Substance abuse history
• Pregnancy, breastfeeding, or unwillingness to use highly effective contraception
• Positive drug or alcohol screen
• Any condition that, in the investigator's judgment, makes participation unsafe or non-feasible